Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroids have been a mainstay of immunosuppressive regimens in renal transplantation despite their adverse effects. The introduction of new immunosuppressant has improved the survival rates and prompted trials of steroid withdrawal. We conducted a randomized prospective study to compare steroid withdrawal at 6 months post-transplant between tacrolimus + mycophenolate mofetil (MMF) (FK group) versus cyclosporine A + MMF (CsA group). Steroid was withdrawn at 6 months post-transplant under the condition of no rejection episode proven by biopsy and maintenance of serum creatinine level <2.0 mg/dl. Fourteen recipients were excluded because of acute rejection within 6 months or protocol violation. Steroid could be tapered off in 62 in FK group and 55 in CsA. Three cases in FK group and five in CsA had acute rejection within another 6 months after steroid withdrawal (P > 0.05). At 12 months, the incidence of post-transplant diabetes was 18.6% vs. 8.0% in FK and CsA group. And hypercholesterolemia was presented in 8.5% vs. 2.0%, hypertension in 47.5% vs. 56.0%, and serum creatinine level 1.18 +/- 0.24 mg/dl vs. 1.18 +/- 0.20 mg/dl, respectively (P > 0.05). Steroid withdrawal may be carried out successfully using both FK and CsA with MMF, but long-term follow-up is necessary.
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PMID:Steroid withdrawal in living donor renal transplant recipients using tacrolimus and cyclosporine: a randomized prospective study. 1677 69

The cerebral vasculature is a target tissue for sex steroid hormones. Estrogens, androgens, and progestins all influence the function and pathophysiology of the cerebral circulation. Estrogen decreases cerebral vascular tone and increases cerebral blood flow by enhancing endothelial-derived nitric oxide and prostacyclin pathways. Testosterone has opposite effects, increasing cerebral artery tone. Cerebrovascular inflammation is suppressed by estrogen but increased by testosterone and progesterone. Evidence suggests that sex steroids also modulate blood-brain barrier permeability. Estrogen has important protective effects on cerebral endothelial cells by increasing mitochondrial efficiency, decreasing free radical production, promoting cell survival, and stimulating angiogenesis. Although much has been learned regarding hormonal effects on brain blood vessels, most studies involve young, healthy animals. It is becoming apparent that hormonal effects may be modified by aging or disease states such as diabetes. Furthermore, effects of testosterone are complicated because this steroid is also converted to estrogen, systemically and possibly within the vessels themselves. Elucidating the impact of sex steroids on the cerebral vasculature is important for understanding male-female differences in stroke and conditions such as menstrual migraine and preeclampsia-related cerebral edema in pregnancy. Cerebrovascular effects of sex steroids also need to be considered in untangling current controversies regarding consequences of hormone replacement therapies and steroid abuse.
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PMID:Influence of sex steroid hormones on cerebrovascular function. 1679 20

Corticosteroids have always played a valuable role in transplantation. Unfortunately, they are subject to a wide range of side effects, such as hyperlipidemia, hypertension, diabetes mellitus, osteoporosis, growth retardation and Cushingoid appearance. Steroids may also exacerbate problems that existed before surgery, including malignancy, hepatitis B and hepatitis C. New, powerful immunosuppressants have allowed steroid use to be reduced or avoided altogether, but use of these regimens is not simple and may be associated with late acute rejection and recurrence of autoimmune disease. The present review examines the rationale for steroid avoidance in liver transplantation and assesses the new regimens that are currently being developed.
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PMID:Steroid avoidance in liver transplantation. 1680 21

This report described an interim analysis of a investigator-driven multicenter trial in renal transplant recipients: the Prospective Quality of life Renal Transplantation Switch Study; Tacrolimus-based immunosuppression ("PQRST study"). Patients included in the trial initially treated with cyclosporine-based immunosuppression after renal transplantation who experienced side effects, such as hypertension, hyperlipidemia, hypertrichosis, or other adverse reactions, were converted to a tacrolimus-based immunosuppressive regimen (n = 31). Steroids were subsequently discontinued between 3 and 6 months after the conversion. As of today 19/31 (50%) patients have been successfully weaned off steroids with the remaining patients in this process. In this interim analysis, with a follow-up ranging from 1 to 18 months both patient and graft survivals were 100%. No patient experienced an acute rejection episode; none of the grafts were lost. Blood pressure decreased in 22/31 (71%) of the patients. No patient developed de novo diabetes or other serious side effect related to the conversion. Three patients were withdrawn from the trial because of side effects: bleeding, depression, and proteinuria. However, none of these adverse events were felt to be directly related to the change of the immunosuppressive regimen to tacrolimus monotherapy. In conclusion, conversion from cyclosporine to tacrolimus-based therapy was safe and well tolerated; it may improve the cardiovascular risk profile after kidney transplantation.
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PMID:Steroid-free immunosuppression in kidney transplant recipients and prograf monotherapy: an interim analysis of a prospective multicenter trial. 1709 29

Approximately two-third of the cases of the adult nephrotic syndrome is caused by a primary glomerular disease, while the remaining one-third is caused by diabetes mellitus, autoimmune diseases, or amyloidosis. There are two different therapies to treat the syndrome: a general and a special treatment. The general treatment includes administering an appropriate diet (reduced intake of proteins and salt), use of diuretics and lipid-lowering drugs (primarily statins) and initiation of anticoagulant treatment, if required. It is generally necessary to administer angiotensin-convertase-enzyme inhibitors and angiotensin receptor blockers as well as initiate a symptomatic treatment to mitigate the loss of special binding-proteins. The special treatment involves the administration of immunosuppressive and cytostatic drugs. This therapy can be initiated only after the evaluation of renal histology and the overall risk status of the patient. Steroids are still the basic immunosuppressive drugs. Their use can be supplemented with other immunosuppressive or cytostatic treatment. In therapy resistant cases, however, new drugs like mycophenolate mofetil or rituximab can also be applied.
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PMID:[Treatment of nephrotic syndrome in the adult]. 1725 32

Activating mutations in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium (KATP) channel is a cause of neonatal diabetes associated with various neurological disorders that include developmental delay, epilepsy, and neonatal diabetes (known together as DEND syndrome). This article reports a girl who developed infantile spasms and early onset diabetes mellitus at the age of 3 months and revealed DEND syndrome with a heterozygous activating mutation in Kir6.2. Infantile spasms with hypsarrhythmia on the electroencephalogram were severe and refractory to steroids. Steroids combined with oral sulfonylurea, a drug that closes the ATP-sensitive potassium channel by an independent mechanism, allowed partial and transitory control of the epilepsy. However, the child still exhibited severe encephalopathy and died of aspiration pneumonia. The role of oral sulfonylurea as an anticonvulsant in DEND syndrome associated with Kir6.2 mutation is discussed.
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PMID:Infantile spasms as an epileptic feature of DEND syndrome associated with an activating mutation in the potassium adenosine triphosphate (ATP) channel, Kir6.2. 1789 Apr 19

Diabetic retinopathy is the leading cause of blindness in developed countries. Diabetic macular edema (DME) is the most frequent cause of vision loss in patients with type 2 diabetes. Steroids may reduce the concentration of inflammatory cytokines and growth factors, and have effect on increased vascular permeability. Topical steroids does not reach intraocular therapeutic concentrations and periocular injection requires frequent injections at the risk of complications. Systemic administration of steroids may be useful, but high doses are required and are associated with severe systemic side effects. Intravitreal injection of steroids provides a powerful therapeutic effect, but it is associated with frequent secondary cataracts and increased IOP. The need for repeated injections may increase the risks associated with the injection procedure. Preliminary studies have proved the possibility of implanting sustained release inserts in the vitreous body, allowing for therapeutic levels of steroids in the vitreous cavity and retina for more than six months. The advantages of these systems are to keep a stable and sustained concentration of the drug with higher therapeutic efficacy thus reducing the number of injections. However, the complications associated with the use of steroids such as cataracts and high IOP are very common.
Curr Diabetes Rev 2009 Feb
PMID:Intravitreal inserts of steroids to treat diabetic macular edema. 1919 95

Cyclosporine A (CsA) is a substrate of P-glycoprotein, an efflux transporter encoded by the ABCB1 gene. Compared with carriers of the wild-type gene, carriers of T allelic variants in exons 21 or 26 have reduced P-glycoprotein activity and, secondarily, increased intracellular concentration of CsA; therefore, carriers of T variants might be at increased risk for CsA-related adverse events. We evaluated the associations between ABCB1 genotypes (in exons 12, 21, and 26) and CsA-related outcomes in 147 renal transplant recipients who were receiving CsA-based immunosuppression and were included in the Mycophenolate Steroids Sparing study. During a median of 65.5 mo follow-up, carriers of T allelic variants in exons 21 or 26 had a three-fold risk for delayed graft function (DGF), a trend to slower recovery of renal function and lower GFR at study end, and significantly higher incidences of new-onset diabetes and cytomegalovirus reactivation compared with carriers of the wild-type genotype. T variants in both exons 21 and 26 were independently associated with 3.8- and 3.5-fold higher risk for DGF, respectively (P = 0.022 and P = 0.034). The incidence of acute rejection and the mean CsA dose and blood levels were comparable in genotype groups. In conclusion, renal transplant recipients with T allelic variants in ABCB1 exons 21 or 26 are at increased risk for CsA-related adverse events. Genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.
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PMID:ABCB1 genotypes predict cyclosporine-related adverse events and kidney allograft outcome. 1947 Jun 83

A 78-year-old man with diabetes mellitus, hyperthyroidism and congestive heart failure was admitted to our hospital because of dyspnea on effort. He had been taking 200 mg/day amiodarone for 2 years, in order to treat a intermitted ventricular tachycardia. His chest X rays showed the appearance of diffuse consolidation in the right lung field. At first severe pulmonary infection was suspected, and he was treated with antibiotics. In spite of the treatment, the chest X-ray findings did not improved. We thought of the possibility of interstitial lung disease, and performed bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) from the right middle lobe. TBLB revealed the organizing pneumonia (OP). At the same time we observed that he had temporary sinus arrest and entered a stated of shock requiring intubation, temporary pacing and intra-aortic balloon pumping (IABP) . The coronary angiography (CAG) revealed no abnormalities and cardiac function was normal. Within two days his sinus rhythm recovered spontaneously. After cessation of amiodarone and administering steroid therapy, pulmonary shadows resolved quickly. Since there were no laboratory signs of connective tissue or infectious disease such as a normal autoimmune serology, antibody titers against Mycoplasma pneumoniae, Clamydia species, and BAL, TBLB cultures, etc, we considered that unilateral organizing pneumonia and temporary sinus arrest could be induced by amiodarone. The amiodarone pulmonary toxicity (APT) commonly courses pleural effusion and while it may be strictly unilateral, there are often diminutive contralateral foci visible on HR-CT. Steroids should be given for months and tapered prudently, otherwise APT may recur owing to the persistence of amiodarone in lung.
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PMID:[Case of unilateral organizing pneumonia induced by amiodarone pulmonary toxicity]. 1951 1

Platelets are circulating cell fragments which play a critical role in thrombosis, and whose activity is associated with the progress of cardiovascular diseases, diabetes, inflammation, and cancer cell metastasis. Recently, a number of nuclear receptors have been found present in human platelets, including the receptors for sex steroids, and glucocorticoids, along with peroxisome proliferator-activated receptors (PPAR)s and retinoid X receptors (RXR)s. Although the platelet contains no nucleus, selective ligands for these receptors activate their respective platelet nuclear receptors and regulate platelet aggregation and activation. The human platelet, because of its abundance and accessibility therefore represents an excellent model system to study the rapid non-genomic mechanism of nuclear receptors. Moreover, since targeting platelets is a major clinical therapeutic area, analysis of platelet nuclear receptors may provide clues for new drug targets as well as provide important information regarding the physiological roles of nuclear receptors in the circulation.
Steroids
PMID:The platelet as a model system for the acute actions of nuclear receptors. 1977 46


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